title: Basic biology of skeletal aging: role of stress response pathways.
abstract: Although a decline in bone formation and loss of bone mass are common features of human aging, the molecular mechanisms mediating these effects have remained unclear. Evidence from pharmacological and genetic studies in mice has provided support for a deleterious effect of oxidative stress in bone and has strengthened the idea that an increase in reactive oxygen species (ROS) with advancing age represents a pathophysiological mechanism underlying age-related bone loss. Mesenchymal stem cells and osteocytes are long-lived cells and, therefore, are more susceptible than other types of bone cells to the molecular changes caused by aging, including increased levels of ROS and decreased autophagy. However, short-lived cells like osteoblast progenitors and mature osteoblasts and osteoclasts are also affected by the altered aged environment characterized by lower levels of sex steroids, increased endogenous glucocorticoids, and higher oxidized lipids. This article reviews current knowledge on the effects of the aging process on bone, with particular emphasis on the role of ROS and autophagy in cells of the osteoblast lineage in mice.
authors.affiliation: Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR 72205. schullermaria@uams.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Almeida
authors.forename: Charles A
authors.initials: CA
authors.lastname: O'Brien
mesh_terms: D050156:Adipogenesis; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence; D005938:Glucocorticoids / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010011:Osteocytes / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D006133:Growth Substances
keywords: Autophagy; Bone; Mesenchymal stem cells; Osteocytes; Oxidative stress.